The present invention relates to the field of catalytic hydrogenation. It devises a method for hydrogenating aryl-azo-pyrimidines to yield the corresponding amino-pyrimidine.
Furst et al., (1957) J. Am. Soc. 79:5492, described successful and convenient reduction of bisaryl-azo compounds to the corresponding hydrazo compounds by hydrazine in the presence of Raney Ni. However, further reductive cleavage to the primary, aromatic amine was found difficult to achieve, being strongly biased by electronic substituent effects and further subject to the irritating and inconvenient observation of requiring particularly dilute reaction mixture. The latter may be accounted for by the fact that Furst's reaction conditions proved not be a transfer hydrogenation reaction but that the metal catalyst only generated the directly reducing reagent, diimide, in situ from the hydrazine by way of a disproportionation reaction as evidenced by the generation of considerable amounts of ammonia during the reaction (Ioffe et al., 1969 J. Org. Chem. USSR 5,1683). The catalyst did not allow of hydrid transfer here.
WO 05/095358 describes a one pot process to catalytically reduce 4,6-dichloro-5-(4-methylphenyl)diazenyl-2-(propylsulfenyl)pyrimidine to 4,6-dichloro-2-(propylthio)-pyrimdin-5-amine. The reaction was carried out in a hydrogenation vessel at 3 bar hydrogen pressure with a biphasic temperature profile, initially allowing of the reduction to the corresponding hydrazo compound at lower temperature and converting the latter to the amine at higher hydrogenation temperature only. The yield obtained was about 80%, apparently improving over the WO 01/92263 from same applicant on the same reaction by virtue of temperature regime. In both patent applications, only the use of noble metal catalysts such as Pt, Pt/V or Pd catalysts is taught.
As a disadvantage, only noble metal catalysts such as Pd or preferably Pt were used, at unusually high catalyst loadings of 10% (w/w). At an industrial scaled process, nobel metal catalysts usually necessitate tiresome recovery and recycling of the catalyst when working up the reaction broth; this is required for sustainable process, since the noble metal raw metals are getting an ever more scarce source. Already, in some areas of technology, supply of some rare metals is already facing exhaustion and hence unavailability of metal itself. Such development has also been forecasted for Pt and Pd. Further, Pd and Pt are particularly liable to poisoning by thioesters and thiols, resulting in increased loading rates. Finally, given the expensive nature of metal catalysts, the yield of the Pt/C catalyzed process await further improvement.
It is the object of the present invention to devise another method of conducting the reducting of said and closely similar 5-diazenyl-pyrimidine to the corresponding 5-amino-pyrimdine.